Studies in this laboratory are designed to elucidate the role of DNA repair processes in human disease, especially in human carcinogenesis and ageing. Most studies have been conducted with cells from patients with xeroderma pigmentosum (XP), all of whom have defective DNA repair plus the clinical abnormalities of premature ageing of the skin and cutaneous malignancies. We measure the DNA excision repair process by assays of UV-induced unscheduled DNA synthesis and are using these assays to study the UV dose response of the excision system and the effect of in vitro ageing on this system. We assess the biological effectiveness of DNA repair with assays of post-irradiation colony-forming ability and have found a striking correlation between the level of effectiveness of DNA repair in XP and the severity of XP-associated neurological abnormalities. We are studying the relationship of UV-induced chromosome abnormalities and of UV-induced mutations to the repair defects of XP. We are extending our work to include cells from patients with other diseases in which DNA repair defects are known or suspected. We have established long-term lymphoblast lines from all six genetic forms or XP which will be a useful tool, especially in biochemical work on the molecular identification of the repair defect.